Joint Laboratory for Translational Medicine Research, Liaocheng People's Hospital, Liaocheng, Shandong, China.
Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, Shandong, China.
PLoS One. 2024 Aug 29;19(8):e0309536. doi: 10.1371/journal.pone.0309536. eCollection 2024.
Biomarkers for classifying and grading gliomas have been extensively explored, whereas populations in public databases were mostly Western/European. Based on public databases cannot accurately represent Chinese population. To identify molecular characteristics associated with clinical outcomes of lower-grade glioma (LGG) and glioblastoma (GBM) in the Chinese population, we performed whole-exome sequencing (WES) in 16 LGG and 35 GBM tumor tissues. TP53 (36/51), TERT (31/51), ATRX (16/51), EFGLAM (14/51), and IDH1 (13/51) were the most common genes harboring mutations. IDH1 mutation (c.G395A; p.R132H) was significantly enriched in LGG, whereas PCDHGA10 mutation (c.A265G; p.I89V) in GBM. IDH1-wildtype and PCDHGA10 mutation were significantly related to poor prognosis. IDH1 is an important biomarker in gliomas, whereas PCDHGA10 mutation has not been reported to correlate with gliomas. Different copy number variations (CNVs) and oncogenic signaling pathways were identified between LGG and GBM. Differential genomic landscapes between LGG and GBM were revealed in the Chinese population, and PCDHGA10, for the first time, was identified as the prognostic factor of gliomas. Our results might provide a basis for molecular classification and identification of diagnostic biomarkers and even potential therapeutic targets for gliomas.
用于分类和分级神经胶质瘤的生物标志物已经得到了广泛的探索,而公共数据库中的人群主要是西方/欧洲人。基于公共数据库的研究结果不能准确代表中国人群。为了确定与中国人群低级别胶质瘤(LGG)和胶质母细胞瘤(GBM)临床结局相关的分子特征,我们对 16 例 LGG 和 35 例 GBM 肿瘤组织进行了全外显子组测序(WES)。TP53(36/51)、TERT(31/51)、ATRX(16/51)、EFGLAM(14/51)和 IDH1(13/51)是最常见的携带突变的基因。IDH1 突变(c.G395A;p.R132H)在 LGG 中明显富集,而 PCDHGA10 突变(c.A265G;p.I89V)在 GBM 中富集。IDH1 野生型和 PCDHGA10 突变与预后不良显著相关。IDH1 是神经胶质瘤的重要生物标志物,而 PCDHGA10 突变与神经胶质瘤无关。LGG 和 GBM 之间存在不同的拷贝数变异(CNVs)和致癌信号通路。在中国人中揭示了 LGG 和 GBM 之间不同的基因组景观,并且首次鉴定 PCDHGA10 为神经胶质瘤的预后因素。我们的研究结果可能为神经胶质瘤的分子分类和诊断生物标志物的鉴定甚至潜在的治疗靶点提供依据。